1. Field of the Invention
The invention generally relates to methods for monitoring the immune response in a patient receiving immunosuppressive drugs. In particular, the invention provides methods based on the measurement of metabolic markers of activation in immune cells as an indicator of the patient's immune response. The methods may be used to predict clinical outcomes and determine treatment courses for patients such as transplant recipients.
2. Background of the Invention
Each year, 55,000 organ transplants are performed worldwide.1 Cumulatively, the number of living organ recipients is now estimated to be over 300,000. Most of these transplant recipients will remain on immunosuppressive drugs for the remainder of their lives to prevent rejection episodes. Controlled doses of these drugs are required to prevent overmedication, which may leave the patient susceptible to opportunistic infection, increased risk of cancer and cardio-vascular disease, and drug toxicity effects, or under-dosing, which may lead to shortened graft survival due to rejection episodes.
The two major drugs used in transplant maintenance today are cyclosporin (Novartis) and Tacrolimus1 (Fujisawa). These drugs are inhibitors of calcineurin, a key enzyme involved in T cell activation.2 Therapeutic drug monitoring (TDM) for these two immunosuppressive drugs is routinely performed, as prescribed by the manufacturers. However, the amount of drug measured in the blood does not directly correlate with the dose of drug administered because of individual pharmacokinetic differences.3 In addition, the level of drug determined by immunoassay is not correlated with immunosuppressive drug efficacy.4 Therefore, the main value of these TDM tests is the avoidance of toxic levels and monitoring patient compliance.
There is currently no method available for the direct assessment of immune status in transplant recipients.